JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-M01 (NP)

 

SIGNALMENT (JPC #1811021): Adult male dog

 

HISTORY: Blood smear from an adult male dog obtained for use by an investigator performing research in leukocyte chemotaxis. Screening test failed to give acceptable baseline results. White cell count - 14,300/mL. Hemogram from Coulter Model S+11 reported 88% lymphocytes, based on distribution of cell size.

 

HISTOPATHOLOGIC DESCRIPTION: Blood smear: The white and red cell counts appear adequate on this good quality smear. The differential count is: segmented neutrophils - 858 (6%), band neutrophils – 7,150 (50%), monocytes – 3,432 (24%), lymphocytes – 1,859 (13%), and eosinophils - 1001 (7%). Neutrophilic band cells are the predominant leukocyte. Over 90% of the granulocytes (neutrophils and eosinophils) have slightly indented round, band-shaped, or bilobed nuclei with smooth nuclear membranes and coarsely clumped (mature) chromatin. There are occasional polychromatophilic erythrocytes, and platelet numbers are adequate.

 

MORPHOLOGIC DIAGNOSIS: Blood smear: Granulocytic hyposegmentation, diffuse, with mature chromatin pattern, breed unspecified, canine.

 

CONDITION: Pelger-Huët anomaly

 

GENERAL DISCUSSION:  

• Pelger-Huët anomaly is an uncommon, usually incidental, autosomal dominant hereditary leukocyte dysplasia that is due to mutations in the lamin B receptor gene (humans and mouse model)
• A familial disorder in which all or most granulocyte (neutrophils, eosinophils, and basophils) and monocyte nuclei fail to undergo segmentation
  1. Bone marrow megakaryocytes are also affected, suggesting the defect occurs at the level of the stem cell
• Condition described in humans, dogs, cats (domestic shorthair), rabbits, a horse, and humans  
• Animals with Pelger-Huët anomaly generally lack any overt functional immune system alterations
  1. One affected family of Foxhounds showed impaired neutrophil and lymphocyte functions (Zablotsky, 2014)

 

PATHOGENESIS:

• Heterozygous phenotype: Most commonly encountered form; animal’s health is not affected, and neutrophils respond normally to function tests (e.g. leukocyte adherence, chemotaxis, phagocytosis, and bactericidal action)
• Homozygous phenotype: Rare and usually lethal in utero; described in rabbits and one stillborn kitten, and often associated with concurrent chondrodysplasias 

 

TYPICAL CLINICAL FINDINGS: None

 

TYPICAL GROSS FINDINGS:

• Usually none
• Homozygous form: Concurrent fetal death, and/or skeletal abnormalities associated with chondrodysplasia

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Circulating cells (granulocytes): Nuclei round or kidney-bean shaped, with normal chromatin condensation and cytoplasmic development
• Uniform appearance and absence of toxic changes (features used to distinguish from the immature cells seen in an inflammatory response)
  1. Pelger-Huët neutrophils should not be classified as band neutrophils (or younger forms), because it will result in a false left shift
• Decreased lobulation of monocyte nuclei has been described, but recognizing it requires an uncommonly used grading system

 

DIFFERENTIAL DIAGNOSIS:

• Other conditions that result in hyposegmented leukocytes in animals
  1. Left shift: Band neutrophils and younger forms have nuclei with less aggregated chromatin and often cytoplasmic toxic changes (e.g. vacuolation, basophilia, Döhle bodies, or toxic granulation); condition does not persistent with treatment  
  2. Pseudo-Pelger-Huët anomaly (acquired Pelger-Huët anomaly): Acquired nuclear hyposegmentation of neutrophils and/or eosinophils described in cattle, dogs and cats; associated with severe inflammation, retroviral infection (e.g., FeLV in cats), chemotherapy, myeloid neoplasia, and myelodysplastic syndrome
• Causes of leukocyte dysplasia: Myelodysplastic or myeloproliferative disorder; Pelger-Huët anomaly; recovery from chemotherapy or severe leukocytopenia 

 

References:

1. Craig LE, Dittmer KE, Thompson KG. Bones and Joints. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:45. 
2. Durham AC, Boes KM. Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:830.
3. Delaney MA, Treuting PM, Rothenburger JL. Lagomorpha. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:482. 
4. Stockham SL, Scott MA. Leukocytes. In: Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 53-106.
5. Valli, VEO, Kiupel M, et al. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:110.
6. Zablotsky SM, Walker DB. Peripheral Blood Smears. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:459, 463. 

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